Tung R M, Blenis J
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Oncogene. 1997 Feb 13;14(6):653-9. doi: 10.1038/sj.onc.1200877.
STE20-homologous proteins have been implicated in mammalian MAP kinase pathways as important transducers of signals from p21 family GTPases. We have cloned a novel STE20 family member, which we call KHS for kinase homologous to SPS1/STE20, that encodes a kinase of 95 kD which is expressed in a variety of tissues. Transiently expressed fusion protein GST-KHS exhibits phosphotransferase activity toward a panel of test substrates, including myelin basic protein (MBP), which is phosphorylated by all known STE20 homologues. KHS is most closely related to another human STE20, GC kinase (74% similar in the catalytic domain), which has recently been placed upstream of the stress-activated MAP kinases (SAPKs/JNKs). KHS also activates JNK in transient coexpression experiments, suggesting a role for KHS in the stress response of fibroblasts. Characterization and comparison of the regulation of these two kinases will be important in elucidating MAP kinase signalling cascades.
STE20同源蛋白作为p21家族GTP酶信号的重要转导因子，已被证实参与哺乳动物丝裂原活化蛋白激酶（MAP激酶）信号通路。我们克隆了一个新的STE20家族成员，因其激酶结构域与SPS1/STE20同源，故将其命名为KHS，它编码一个95kD的激酶，在多种组织中表达。瞬时表达的融合蛋白GST-KHS对包括髓鞘碱性蛋白（MBP）在内的一系列测试底物表现出磷酸转移酶活性，所有已知的STE20同源物均可使MBP磷酸化。KHS与另一种人类STE20，即GC激酶（催化结构域中74%相似）关系最为密切，GC激酶最近被定位在应激激活的MAP激酶（SAPKs/JNKs）上游。在瞬时共表达实验中，KHS也能激活JNK，这表明KHS在成纤维细胞应激反应中发挥作用。对这两种激酶调控机制的表征和比较，对于阐明MAP激酶信号级联反应具有重要意义。
